Salt experienced a paradigm shift when excess sodium intake was correlated to elevated cardiovascular diseases. To efficiently reduce sodium levels in food products without compromising in salt taste quality, it is key to understand peri-receptor mechanisms affecting salt taste perception within the oral cavity. The present study could demonstrate that the salivary proteolytic activity plays a crucial role in fine-tuning salt taste sensitivity. In doing so, saliva samples of highly insensitive panellists were found to be enriched in endopeptidase inhibitor activity whereas highly sensitive panellists demonstrated an increased endopeptidase activity. At the same time, a serine-type endopeptidase was shown for the first time to exhibit a salt taste enhancing effect upon oral administration which could be assigned to an in-vivo release of tetrapeptide PLWR through digestive salivary processes.